KEY ISSUES IN = SURGICAL MANAGEMENT OF RENAL TUMORS

KEY=20 ISSUES IN SURGICAL MANAGEMENT OF RENAL TUMORS

Sandeep=20 gupta, Shailesh A Shah

Institute=20 Of Kidney diseases & Research Centre, Ahmedabad, = India

INTRODUCTION:=20 Renal tumors have been variously classified by different authors. But = for the=20 treating surgeon the key issue is to differentiate solid from cystic = tumors and=20 most importantly benign from malignant tumors.

DIAGNOSIS:=20 Ultrasonography is reliable for differentiating solid tissue from fluid = and can=20 establish the diagnosis of a simple renal cyst. Strict sonographic = criteria for=20 simple cysts include a smooth cyst wall, a round or oval shape without = internal=20 echoes, and thorough transmission with strong acoustic shadows = posteriorly. If=20 these criteria are met, observation is sufficient in an asymptomatic = patient. A=20 renal mass that is not clearly a simple cyst by strict ultrasound = criteria=20 should be evaluated further with computed tomography (CT) scanning. Any renal mass that = enhances=20 with intravenous contrast on CT scanning should be considered a renal = cell=20 carcinoma (RCC). The differentiation between a benign renal = cyst and=20 a cystic RCC is difficult. Bosniak has=20 developed a classification scheme that divides renal cystic lesions into = four=20 categories that are differ in terms of the likelihood of = malignancy (Bosniak, 1997).

Category

Characteristics=20 Of Renal Cysts

Management

Simple=20 Benign Cyst

No=20 Treatment In Asymptomatic Patient

Minimally=20 complicated Cyst

Invariably=20 Benign

Follow=20 Up With periodic imaging

III

More=20 Complicated cyst

Indeterminate

Surgical=20 Exploration

Invariably=20 Cystic RCCs

Surgical=20 Exploration

DIFFERENTIAL=20 DIAGNOSIS: For radiographically detected solid renal masses, the = differential=20 diagnosis includes RCC, renal adenoma, oncocytoma, AML, transitional = cell=20 carcinoma, metastatic tumor, abscess, infarct, vascular malformation, or = renal=20 pseudo tumor. The diagnosis of most of these lesions can be established = on the=20 basis of the clinical presentation and the characteristic radiographic = features.=20 However, it is not possible = to reliably=20 distinguish RCC, adenoma, and oncocytoma.

SURGICAL=20 MANAGEMENT: Given these=20 uncertainties, most authors emphasize to treat these tumors with = exploration and=20 nephron-sparing surgery or radical nephrectomy, depending on the = clinical=20 circumstances=20 (Licht, 1995).

ANGIOMYOLIPOMA: = AML is a benign neoplasm that consists of adipose tissue, smooth muscle, = and=20 vessels. Massive retroperitoneal hemorrhage from AML, also known as = Wunderlich's=20 syndrome, represents the most feared complication=20 (Oesterling et al, 1986). The presence of even a small = amount of fat=20 within a renal lesion on CT scan (confirmed by Hounsfield units = ≤10) virtually=20 excludes the diagnosis of RCC (Bosniak et al, 1998). Smaller AMLs (less than 4 cm), can = be followed=20 expectantly, with repeat evaluation and imaging at 6- to 12-month = intervals. For=20 larger and symptomatic tumors intervention should be done in the form of = total=20 nephrectomy or partial nephrectomy or selective embolisation.

Renal=20 Cell Carcinoma:

RCC,=20 which accounts for 3% of all = adult=20 malignancies, is primarily a disease of the elderly patient, with = typical=20 presentation in the sixth and seventh decades of life with a = male-to-female=20 predominance of 3 to 2 (Landis et al, 1999).

CLINICAL=20 PRESENTATION: With the = routine use of=20 ultrasonography for the evaluation of nonspecific symptoms more than 50% = of RCCs=20 are now detected incidentally. Symptoms associated with RCC are = due to=20 local tumor growth, hemorrhage, paraneoplastic syndromes, or metastatic=20 disease. The classic triad of = flank=20 pain, gross hematuria, and palpable abdominal mass is now rarely = found=20 and denotes advanced disease, and referred as the "too late=20 triad.

STAGING=20 OF RCC:The clinical staging of RCC begins with a history, physical = examination,=20 and laboratory tests. Symptomatic=20 presentation, significant weight loss (>10% of body weight), bone = pain, and=20 poor performance status suggest advanced disease as do a palpable mass = or=20 lymphadenopathy. A nonreducing varicocele and a lower extremity edema = suggest=20 venous involvement. (Srigley et al, 1997).The radiographic = staging of=20 RCC is done with a high-quality thin slice CT scan and a routine chest=20 radiograph (Bechtod & Zagoria, 1997). MRI is = reserved=20 for patients with locally advanced malignancy, venous involvement, renal = insufficiency, or allergy to intravenous contrast (Choyke, 1997). MRI provides = information about=20 both the cephalad and the caudad extent of the IVC thrombus and can = distinguish=20 bland from tumor thrombus. = Metastatic=20 evaluation should include a chest radiograph, abdominal and pelvic CT, = and liver=20 function tests. A bone scan can be reserved for patients with = elevated=20 serum alkaline phosphatase or bone pain and a chest CT scan for patients = with=20 pulmonary symptoms or an abnormal chest radiograph (Lim & Carter, 1993).In 1997, the International Union = Against=20 Cancer and the American Joint Committee on Cancer proposed a revision of = the=20 TNM=20 system that is now the recommended staging system for RCC=20 (Guinan et al, = 1997).

Treatment=20 of Localized Renal Cell Carcinoma:

RADICAL=20 NEPHRECTOMY: The=20 objective of surgical therapy is to excise all tumor with an adequate = surgical=20 margin. Robson (1969) established radical = nephrectomy as=20 the "gold standard" curative operation for localized RCC. Recent reports = indicate 5-year survival rates of 75% or more for stage I (T1=96T2) RCC. = Radical=20 nephrectomy encompasses early ligation of the renal vessels, removal of = the=20 kidney outside Gerota's fascia, removal of ipsilateral adrenal gland, = and=20 performance of a complete regional lymphadenectomy from crus of the = diaphragm to=20 aortic bifurcation. = The=20 operation is usually performed through a transperitoneal incision to = allow=20 abdominal exploration for metastatic disease and early access to the = renal=20 vessels with minimal manipulation of the tumor. We prefer an extended = subcostal=20 or a bilateral subcostal incision. The thoracoabdominal approach is used = for=20 patients with large tumors in upper portion of the kidney. Laparoscopic radical nephrectomy is = an=20 alternative in the management of low-volume (8 cm or smaller), localized = RCCs=20 with no local invasion, renal vein involvement, or = lymphadenopathy. Early=20 data suggest that cancer-specific survival after laparoscopic radical=20 nephrectomy is comparable to that after open surgery (Cadeddu et al, = 1998).

CONTROVERSIES:=20 Controversy has arisen = concerning the=20 need for some of these practices in all patients. Removal of = adrenal=20 gland is not routinely necessary in the absence of radiographic adrenal=20 enlargement unless the malignancy either extensively involves the kidney = or is=20 located in the upper portion of the kidney (Sagalowsky et al, 1994).Several = characteristics=20 of RCC argue against a therapeutic role for lymphadenectomy. First, the = tumor=20 metastasizes through the blood stream and the lymphatic system with = equal=20 frequency, Second, the lymphatic drainage of the kidney is variable, and = even an=20 extensive retroperitoneal dissection cannot be expected to remove all = possible=20 metastasis. Third, many patients without metastases to regional lymph = nodes=20 develop disseminated metastases. Nevertheless, current data do suggest = that a=20 subset of patients with micrometastatic lymph node involvement benefit = (Golimbu et al, 1986). In all = likelihood, the=20 involved lymph nodes in these patients would be removed by a radical=20 nephrectomy.

FOLLOW=20 UP: Studies have demonstrated that the risk of postoperative recurrent=20 malignancy is stage dependent (Sandock=20 et al, 1995; Levy=20 et al, 1998). Thus a=20 cost-effective surveillance for = recurrent=20 malignancy can be tailored according to the tumor = stage.

Pathologic=20 stage

History,=20 Examination & Blood Tests

Chest=20 X-ray

Abdominal=20 CT Scan

T1N0M0

Yearly=20

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--------

T2N0M0

Yearly

Every=20 2 Years

T3abcN0M0

Every=20 6 Months For 3 Years, Then Yearly

At=20 1 Year, Then Every 2 = Years

NEPHRON-SPARING = SURGERY: Nephron-sparing=20 surgery entails complete local resection of a renal tumor while leaving = the=20 largest possible amount of normal functioning parenchyma in the involved = kidney. Accepted indications = for=20 nephron-sparing surgery include situations in which radical = nephrectomy=20 would render the patient anephric with a subsequent immediate need for = dialysis.=20 This includes patients with = bilateral=20 RCC or RCC involving a solitary functioning kidney e.g unilateral = renal=20 agenesis, prior removal of the contralateral kidney, or irreversible = impairment=20 of contralateral renal function by a benign disorder. Another indication = is=20 represented by patients with = unilateral=20 carcinoma and a functioning opposite kidney affected by a condition that = might=20 threaten its future function such as renal artery stenosis (Campbell et al, 1993), hydronephrosis, chronic = pyelonephritis,=20 ureteral reflux, calculus disease, diabetes and nephrosclerosis. Studies = have=20 reported cancer-specific survival rates of 78% to 100% in such patients=20 (comparable to radical nephrectomy). The major disadvantage is = postoperative=20 local tumor recurrence (LTR) in the operated kidney, (10% = incidence).=20 This is likely a manifestation of undetected microscopic multifocal RCC = in the=20 renal remnant. The surveillance for=20 recurrent malignancy after nephron-sparing surgery can also be tailored=20 according to the initial pathologic tumor = stage.

Pathologic=20 Stage

History,=20 Examination & Blood Tests

Chest=20 X-ray

Abdominal=20 CT Scan

T1N0M0

Yearly=20

-------

--------

T2N0M0

Yearly

Every=20 2 Years

T3abcN0M0

Every=20 6 Months For 3Years, Then Yearly

Every=20 6 Months For 3 Years, Then Yearly

Every=20 6 Months For 3 Years, Then=20 Yearly

Patients=20 who undergo nephron-sparing surgery are at risk for developing long-term = hyperfiltration renal injury. Because proteinuria is the initial = manifestation=20 of the phenomenon, a 24-hour urinary protein measurement should be = obtained=20 yearly in these patients.

NEPHRON-SPARING = SURGERY WITH NORMAL OPPOSITE KIDNEY: Although=20 radical nephrectomy remains the standard treatment for localized renal = carcinoma=20 in patients with a normal opposite kidney, a number of authors have = reported=20 excellent results with nephron-sparing surgery in this setting. Cancer-specific survival ranges from = 90% to=20 100%, and there have been only 12 cases of postoperative tumor = recurrence (2%).=20 Significantly, the mean tumor size in most of these reports was less = than 4=20 cm. This data suggests that nephron-sparing surgery may be an = acceptable=20 therapeutic approach in patients who have a single, small (less than 4 = cm) RCC=20 and a normal contralateral kidney.

RENAL=20 CRYOSURGERY: Renal cryosurgery is an emerging nephron-sparing treatment = option=20 for RCC. Established prerequisites for successful cryosurgery include = rapid=20 freezing, gradual thawing, and a repetition of freeze-thaw cycle. The = targeted=20 diseased tissue, with a surrounding margin of healthy parenchyma, is = rapidly=20 frozen in situ. This devitalized tissue is then allowed to spontaneously = slough=20 over time, with healing by secondary granulation=20 (Gill & Novick, 1999). Clinical renal cryoablation has = been=20 performed by open, percutaneous, and laparoscopic techniques. During = clinical=20 laparoscopic renal cryoablation, intraoperative laparoscopic ultrasound = is a=20 reliable and vital imaging technique. Meticulous long-term follow-up of = patients=20 is critical for determining local recurrence and cancer-free survival = rates=20 after renal cryoablation.

OBSERVATION:=20 Bosniak's data suggest that patients with small, solid, enhancing,=20 well-marginated, homogeneous renal lesions, who are elderly or poor = surgical=20 risks, can safely be managed with observation and serial renal imaging = at=20 6-month or 1-year intervals. This approach would not be appropriate for = patients=20 with larger (greater than 3 cm), poorly marginated, or nonhomogeneous = solid=20 renal lesions or younger, otherwise healthy patients with small, solid = tumors=20 even=20 if these lesions are less than 3 cm.

Treatment=20 of Locally Advanced Renal Cell Carcinoma

INFERIOR=20 VENA CAVAL INVOLVEMENT: Although=20 IVC involvement renders complete surgical excision more complicated, = surgery=20 offers the only cure when there are no lymph nodes or metastases. For these patients 5-year survival = rates of=20 47% to 69% have been reported. The presence of lymph node or distant = metastases=20 carries a dismal prognosis that is not altered by radical surgical=20 extirpation. The prognostic significance of the cephalad extent = of an=20 inferior vena caval tumor thrombus has been controversial. There may be = a=20 palliative role for surgery in some patients with metastasis who = experience=20 severe disability from intractable edema, ascites, cardiac dysfunction, = or local=20 symptoms such as abdominal pain or hematuria.

LOCALLY=20 INVASIVE RENAL CELL CARCINOMA: =20 Occasionally=20 patients harbor large tumors that invade adjacent structures and present with pain. = Intrahepatic=20 metastases occur more often than local extension. The propensity for = tumors to=20 parasitize vessels may account for extension into the large bowel, = mesentery,=20 and colon. Because surgical therapy is the only effective management for = this=20 tumor, extended operations are sometimes indicated. Complete excision of = the=20 tumor, including excision of the involved bowel, spleen, or abdominal = wall=20 muscles, is the aim of therapy. Partial excision of the large primary = tumor, or=20 debulking, is rarely indicated.

LOCAL=20 RECURRENCE AFTER RADICAL NEPHRECTOMY OR PARTIAL NEPHRECTOMY: = Advanced=20 stage T patients with positive lymph nodes are at increased risk of = renal fossa=20 recurrence. Local recurrence after radical nephrectomy is quite rare in = patients=20 with low-stage T1=96T2 N0M0 RCC. In=20 patients with isolated local recurrence of RCC after radical nephrectomy = and no=20 metastatic disease, surgical excision remains the preferred treatment = (Esrig et al, 1992). Radiation therapy = may be of=20 value for palliation of symptomatic local recurrences in unfit patients. = Patients who develop local recurrence in the remnant kidney after = nephron-sparing=20 surgery with no metastasis may be considered for secondary = surgical=20 treatment. In some cases, another partial nephrectomy can be done. If = this is=20 not possible, total nephrectomy with initiation of chronic dialysis and=20 subsequent renal transplantation is an = alternative.

Treatment=20 of Metastatic Renal Cell Carcinoma:

NEPHRECTOMY:=20 Early=20 reports suggested that removal of the primary tumor could induce = regression of=20 metastatic lesions. However, such regression occurs in less than 1% of = patients;=20 therefore, this approach has been abandoned. Palliative nephrectomy is=20 occasionally indicated in patients with severe hemorrhage, severe pain,=20 paraneoplastic syndromes, or compression of adjacent viscera.=20

HORMONAL=20 THERAPY: Hormonal therapy has poor results for metastatic = RCC=20 (Harris, 1983).

CHEMOTHERAPY:=20 Studies have demonstrated that RCC is chemoresistant (Yagoda (1995).

RADIATION=20 THERAPY: Radiation therapy has been used as adjuvant treatment after = radical=20 nephrectomy and for palliation of metastatic = lesions.

IMMUNOBIOLOGIC=20 THERAPY: This=20 represent an encouraging pathway for the treatment of metastatic RCC. = The most popular therapies have been = interferon and interleukins.

MULTIMODALITY THERAPY:=20 One rationale for the use of multimodality therapy is to surgically = decrease=20 tumor burden and thereby enhance the response to immunotherapy. Various=20 approaches for multimodality therapy include (1) initial adjuvant = nephrectomy=20 followed by immunotherapy, (2) initial immunotherapy followed by = adjuvant=20 nephrectomy for responders, and (3) nephrectomy and immunotherapy = followed by=20 resection of residual or recurrent metastatic lesions. Randomized = clinical=20 trials are needed to validate these approaches.

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